tbuckley/cabot-search huggingface dataset:
Left Ventricular Filling Pressure in Chronic Thromboembolic Pulmonary Hypertension
Authors: Christian Gerges, Anna-Maria Pistritto, Mario Gerges, Richard Friewald, Valerie Hartig, Thomas M. Hofbauer, Benedikt Reil, Leon Engel, Varius Dannenberg, Stefan P. Kastl, Nika Skoro-Sajer, Bernhard Moser, Shahrokh Taghavi, Walter Klepetko, Irene M. Lang
Journal: Journal of the American College of Cardiology (2023)

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by obstruction of major pulmonary arteries with organized thrombi. Clinical risk factors for pulmonary hypertension due to left heart disease including metabolic syndrome, left-sided valvular heart disease, and ischemic heart disease are common in CTEPH patients. The authors sought to investigate prevalence and prognostic implications of elevated left ventricular filling pressures (LVFP) in CTEPH. A total of 593 consecutive CTEPH patients undergoing a first diagnostic right and left heart catheterization were included in this study. Mean pulmonary arterial wedge pressure (mPAWP) and left ventricular end-diastolic pressure (LVEDP) were utilized for assessment of LVFP. Two cutoffs were applied to identify patients with elevated LVFP: 1) for the primary analysis mPAWP and/or LVEDP >15 mm Hg, as recommended by the current pulmonary hypertension guidelines; and 2) for the secondary analysis mPAWP and/or LVEDP >11 mm Hg, representing the upper limit of normal. Clinical and echocardiographic features, and long-term mortality were assessed. LVFP was >15 mm Hg in 63 (10.6%) and >11 mm Hg in 222 patients (37.4%). Univariable logistic regression analysis identified age, systemic hypertension, diabetes, atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume as significant predictors of elevated LVFP. Atrial fibrillation, calcific aortic valve stenosis, mitral regurgitation, and left atrial volume remained independent determinants of LVFP in adjusted analysis. At follow-up, higher LVFPs were measured in patients who had meanwhile undergone pulmonary endarterectomy (P = 0.002). LVFP >15 mm Hg (P = 0.021) and >11 mm Hg (P = 0.006) were both associated with worse long-term survival. Elevated LVFP is common, appears to be due to comorbid left heart disease, and predicts prognosis in CTEPH.
Incidence of Atherosclerotic Cardiovascular Disease in Young Adults at Low Short-Term But High Long-Term Risk
Authors: Jaejin An, Yiyi Zhang, Hui Zhou, Mengnan Zhou, Monika M. Safford, Paul Muntner, Andrew E. Moran, Kristi Reynolds
Journal: Journal of the American College of Cardiology (2023)

Young adults may have high long-term atherosclerotic cardiovascular disease (ASCVD) risk despite low short-term risk. In this study, we sought to compare the performance of short-term and long-term ASCVD risk prediction tools in young adults and evaluate ASCVD incidence associated with predicted short-term and long-term risk. We included adults aged 18 to 39 years, from 2008 to 2009 in a U.S. integrated health care system, and followed them through 2019. We calculated 10-year and 30-year ASCVD predicted risk and assessed ASCVD incidence. Among 414,260 young adults, 813 had an incident ASCVD event during a median of 4 years (maximum 11 years). Compared with 10-year predicted risk, 30-year predicted risk improved reclassification (net reclassification index: 16%) despite having similar discrimination (Harrell's C: 0.749 vs 0.726). Overall, 1.0% and 2.2% of young adults were categorized as having elevated 10-year (≥7.5%) and elevated 30-year (≥20%) predicted risk, respectively, and 1.6% as having low 10-year (<7.5%) but elevated 30-year predicted risk. The ASCVD incidence rate per 1,000 person-years was 2.60 (95% CI: 1.92-3.52) for those with elevated 10-year predicted risk, 1.87 (95% CI: 1.42-2.46) for those with low 10-year but elevated 30-year predicted risk, and 0.32 (95% CI: 0.30-0.35) for those with low 10-year and 30-year predicted risk. The age- and sex-adjusted incidence rate ratio was 3.04 (95% CI: 2.25-4.10) comparing those with low 10-year but elevated 30-year predicted risk and those with low 10-year and 30-year predicted risk. Long-term ASCVD risk prediction tools further discriminate a subgroup of young adults with elevated observed risk despite low estimated short-term risk.
Right Ventricular Reverse Remodeling After Transcatheter Tricuspid Valve Replacement in Patients With Heart Failure
Authors: Ludwig T. Weckbach, Lukas Stolz, Andrew G. Chatfield, Neil P. Fam, Ralph Stephan von Bardeleben, Charles J. Davidson, Rebecca T. Hahn, Jörg Hausleiter
Journal: Journal of the American College of Cardiology (2023)
Audio Summary
Journal: Journal of the American College of Cardiology (2023)

Mental illness among physicians is an increasingly recognized concern. Global data on mental health conditions (MHCs) among cardiologists are limited.The purpose of this study was to investigate the global prevalence of MHCs among cardiologists and its relationships to professional life.The American College of Cardiology conducted an online survey with 5,931 cardiologists globally in 2019. Data on demographics, practice, MHC, and association with professional activities were analyzed. The P values were calculated using the chi-square, Fischer exact, and Mann-Whitney U tests. Univariate and multivariate logistic regression analysis determined the association of characteristics with MHC.Globally, 1 in 4 cardiologists experience any self-reported MHC, including psychological distress, or major or other psychiatric disorder. There is significant geographic variation in MHCs, with highest and lowest prevalences in South America (39.3%) and Asia (20.1%) (P < 0.001). Predictors of MHCs included experiencing emotional harassment (OR: 2.81; 95% CI: 2.46-3.20), discrimination (OR: 1.85; 95% CI: 1.61-2.12), being divorced (OR: 1.85; 95% CI: 1.27-2.36), and age <55 years (OR: 1.43; 95% CI: 1.24-1.66). Women were more likely to consider suicide within the past 12 months (3.8% vs 2.3%), but were also more likely to seek help (42.3% vs 31.1%) as compared with men (all P < 0.001). Nearly one-half of cardiologists reporting MHCs (44%) felt dissatisfied on at least one professional metric including feeling valued, treated fairly, and adequate compensation.More than 1 in 4 cardiologists experience self-reported MHCs globally, and the association with adverse experiences in professional life is substantial. Dedicated efforts toward prevention and treatment are needed to maximize the contributions of affected cardiologists.
Association Between Number of Volunteer Responders and Interventions Before Ambulance Arrival for Cardiac Arrest
Authors: Mads Christian Tofte Gregers, Linn Andelius, Julie Samsoee Kjoelbye, Anne Juul Grabmayr, Louise Kollander Jakobsen, Nanna Bo Christensen, Astrid Rolin Kragh, Carolina Malta Hansen, Rasmus Meyer Lyngby, Ulla Væggemose, Christian Torp-Pedersen, Annette Kjær Ersbøll, Fredrik Folke
Journal: Journal of the American College of Cardiology (2023)

Volunteer responder (VR) programs for activation of laypersons in out-of-hospital cardiac arrest (OHCA) have been deployed worldwide, but the optimal number of VRs to dispatch is unknown. The purpose of this study was to investigate the association between the number of VRs arriving before Emergency Medical Services (EMS) and the proportion of bystander cardiopulmonary resuscitation (CPR) and defibrillation. We included OHCAs not witnessed by EMS with VR activation from the Capital Region (September 2, 2017, to May 14, 2019) and the Central Region of Denmark (November 5, 2018, to December 31, 2019). We created 4 groups according to the number of VRs arriving before EMS: 0, 1, 2, and 3 or more. Using a logistic regression model adjusted for EMS response time, we examined associations between the number of VRs arriving before EMS and bystander CPR and defibrillation. We included 906 OHCAs. The adjusted ORs for bystander CPR were 2.40 (95% CI: 1.42-4.05), 3.18 (95% CI: 1.39-7.26), and 2.70 (95% CI: 1.32-5.52) when 1, 2, or 3 or more VRs arrived before EMS (reference), respectively. The adjusted OR for bystander defibrillation increased when 1 (1.97 [95% CI: 1.12-3.52]), 2 (2.88 [95% CI: 1.48-5.58]), or 3 or more (3.85 [95% CI: 2.11-7.01]) VRs arrived before EMS (reference). The adjusted OR of bystander defibrillation increased to 1.95 (95% CI: 1.18-3.22) when ≥3 VRs arrived first compared with 1 VR arriving first (reference). We found an association of increased bystander CPR and defibrillation when 1 or more VRs arrived before the EMS with a trend toward increased bystander defibrillation with increasing number of VRs arriving first.
Optimizing Prepregnancy Cardiovascular Health to Improve Outcomes in Pregnant and Postpartum Individuals and Offspring: A Scientific Statement From the American Heart Association
Authors: Sadiya S. Khan, LaPrincess C. Brewer, Mary M. Canobbio, Marilyn J. Cipolla, William A. Grobman, Jennifer Lewey, Erin D. Michos, Eliza C. Miller, Amanda M. Perak, Gina S. Wei, Holly Gooding
Journal: Circulation (2023)

This scientific statement summarizes the available preclinical, epidemiological, and clinical trial evidence that supports the contributions of prepregnancy (and interpregnancy) cardiovascular health to risk of adverse pregnancy outcomes and cardiovascular disease in birthing individuals and offspring. Unfavorable cardiovascular health, as originally defined by the American Heart Association in 2010 and revised in 2022, is prevalent in reproductive-aged individuals. Significant disparities exist in ideal cardiovascular health by race and ethnicity, socioeconomic status, and geography. Because the biological processes leading to adverse pregnancy outcomes begin before conception, interventions focused only during pregnancy may have limited impact on both the pregnant individual and offspring. Therefore, focused attention on the prepregnancy period as a critical life period for optimization of cardiovascular health is needed. This scientific statement applies a life course and intergenerational framework to measure, modify, and monitor prepregnancy cardiovascular health. All clinicians who interact with pregnancy-capable individuals can emphasize optimization of cardiovascular health beginning early in childhood. Clinical trials are needed to investigate prepregnancy interventions to comprehensively target cardiovascular health. Beyond individual-level interventions, community-level interventions must include and engage key stakeholders (eg, community leaders, birthing individuals, families) and target a broad range of antecedent psychosocial and social determinants. In addition, policy-level changes are needed to dismantle structural racism and to improve equitable and high-quality health care delivery because many reproductive-aged individuals have inadequate, fragmented health care before and after pregnancy and between pregnancies (interpregnancy). Leveraging these opportunities to target cardiovascular health has the potential to improve health across the life course and for subsequent generations.
Comparative Effectiveness of Left Atrial Appendage Occlusion Versus Oral Anticoagulation by Sex
Authors: Emily P. Zeitler, Stephen Kearing, Megan Coylewright, Devi Nair, Jonathan C. Hsu, Douglas Darden, A. James O’Malley, Andrea M. Russo, Sana M. Al-Khatib
Journal: Circulation (2023)

The comparative real-world outcomes of older patients with atrial fibrillation (AF) treated with anticoagulation compared with left atrial appendage occlusion (LAAO) may be different from those in clinical trials because of differences in anticoagulation strategies and patient demographics, including a greater proportion of women. We sought to compare real-world outcomes between older patients with AF treated with anticoagulation and those treated with LAAO by sex.Using Medicare claims data from 2015 to 2019, we identified LAAO-eligible beneficiaries and divided them into sex subgroups. Patients receiving LAAO were matched 1:1 to those receiving anticoagulation alone through propensity score matching. The risks of mortality, stroke or systemic embolism, and bleeding were compared between matched groups with adjustment for potential confounding characteristics in Cox proportional hazards models.Among women, 4085 LAAO recipients were matched 1:1 to those receiving anticoagulation; among men, 5378 LAAO recipients were similarly matched. LAAO was associated with a significant reduction in the risk of mortality for women and men (hazard ratio [HR], 0.509 [95% CI, 0.447-0.580]; and HR, 0.541 [95% CI, 0.487-0.601], respectively; P<0.0001), with a similar finding for stroke or systemic embolism (HR, 0.655 [95% CI, 0.555-0.772]; and HR, 0.649 [95% CI, 0.552-0.762], respectively; P<0.0001). Bleeding risk was significantly greater in LAAO recipients early after implantation but lower after the 6-week periprocedural period for women and men (HR, 0.772 [95% CI, 0.676-0.882]; and HR, 0.881 [95% CI, 0.784-0.989], respectively; P<0.05).In a real-world population of older Medicare beneficiaries with AF, compared with anticoagulation, LAAO was associated with a reduction in the risk of death, stroke, and long-term bleeding among women and men. These findings should be incorporated into shared decision-making with patients considering strategies for reduction in AF-related stroke.
Sex Differences in 10-Year Outcomes After Percutaneous Coronary Intervention With Drug-Eluting Stents: Insights From the DECADE Cooperation
Authors: J.J. Coughlan, Lorenz Räber, Salvatore Brugaletta, Sebastian Kufner, Michael Maeng, Lisette Okkels Jensen, Luis Ortega-Paz, Sarah Bär, Karl-Ludwig Laugwitz, Morten Madsen, Dik Heg, Alp Aytekin, Stephan Windecker, Kevin Kris Warnakula Olesen, Manel Sabaté, Adnan Kastrati, Salvatore Cassese
Journal: Circulation (2023)

Although some studies have investigated sex-related outcomes up to 5 years after percutaneous coronary intervention (PCI), analyses at longer follow-up (ie, to 10 years) in large cohorts treated exclusively with drug-eluting stent (DES) platforms are lacking. Therefore, this study aimed to define whether sex-related differences in long-term outcomes after PCI persist both in the DES era and at longer-term follow-up.Individual data of patients treated with DES in 5 randomized controlled trials with 10-year follow-up were pooled. Patients were divided into 2 groups by sex. The analysis of individual participant data was performed using a 1-stage approach by entering a clustering effect by parent study in all univariable and multivariable models focusing on sex. The main outcomes of interest for this analysis included cardiovascular death, myocardial infarction, repeat revascularization, and definite stent thrombosis to 10 years after PCI. Survival was analyzed by the Kaplan-Meier method to estimate the time to first event, and differences between the 2 groups were tested with the log-rank test. Hazard ratios (HRs) and 95% CIs were calculated with a Cox proportional hazards model. Conventional multivariable analyses with adjustment for relevant variables were performed.Among 9700 patients undergoing PCI with DES implantation included in the present analysis, 2296 were women and 7404 were men. Through to 10 years, cardiovascular death occurred in 407 of the 2296 female patients and 1012 of the 7404 male patients (adjusted HR [HRadj], 0.94 [95% CI, 0.80-1.11]). Female sex was associated with a lower risk of repeat revascularization of the target lesion (HRadj, 0.80 [95% CI, 0.74-0.87]), target vessel (HRadj, 0.81 [95% CI, 0.76-0.87]), and nontarget vessels (HRadj, 0.69 [95% CI, 0.62-0.77]). Compared with male patients, female patients displayed an increased risk of myocardial infarction in the first 30 days after PCI with DES (HRadj, 1.65 [95% CI, 1.24-2.19]) but a comparable risk of myocardial infarction thereafter. The risk of definite stent thrombosis was not significantly different between female and male patients (HRadj, 1.14 [95% CI, 0.89-1.47]).Through to 10-year follow-up after PCI with DES, female patients are at increased risk of early myocardial infarction, receive fewer repeat revascularizations, and have no difference in cardiovascular mortality compared with male patients.
Rethinking Menopausal Hormone Therapy: For Whom, What, When, and How Long?
Authors: Leslie Cho, Andrew M. Kaunitz, Stephanie S. Faubion, Sharonne N. Hayes, Emily S. Lau, Nicole Pristera, Nandita Scott, Jan L. Shifren, Chrisandra L. Shufelt, Cynthia A. Stuenkel, Kathryn J. Lindley
Journal: Circulation (2023)

Menopausal hormone therapy (HT) was widely used in the past, but with the publication of seminal primary and secondary prevention trials that reported an excess cardiovascular risk with combined estrogen-progestin, HT use declined significantly. However, over the past 20 years, much has been learned about the relationship between the timing of HT use with respect to age and time since menopause, HT route of administration, and cardiovascular disease risk. Four leading medical societies recommend HT for the treatment of menopausal women with bothersome menopausal symptoms. In this context, this review, led by the American College of Cardiology Cardiolovascular Disease in Women Committee, along with leading gynecologists, women's health internists, and endocrinologists, aims to provide guidance on HT use, including the selection of patients and HT formulation with a focus on caring for symptomatic women with cardiovascular disease risk.
Long-Term Adverse Outcomes in Black Women With Ischemia and No Obstructive Coronary Artery Disease: A Study of the WISE (Women’s Ischemia Syndrome Evaluation) Cohort
Authors: Judy M. Luu, Pankaj Malhotra, Galen Cook-Wiens, Carl J. Pepine, Eileen M. Handberg, Steven E. Reis, Nathaniel Reichek, Vera Bittner, Janet Wei, Sheryl F. Kelsey, Reddy Sailaja Marpuri, George Sopko, C. Noel Bairey Merz
Journal: Circulation (2023)
A rapid realist review of universal interventions to promote inclusivity and acceptance of diverse sexual and gender identities in schools
Authors: Merle Schlief, Theodora Stefanidou, Talen Wright, Grace Levy, Alexandra Pitman, Gemma Lewis
Journal: Nature Human Behaviour (2023)

Abstract Universal interventions to promote inclusivity and acceptance of diverse sexual and gender identities in schools could help to prevent mental health problems in this population. We reviewed evidence and developed programme theories to explain which universal interventions work, for whom, in which contexts and why. We conducted a rapid realist review and extracted data in context–mechanism–outcome configurations, to develop and refine programme theories. We included 53 sources and identified five intervention themes: student pride clubs, inclusive antibullying and harassment policies, inclusive curricula, workshops and staff training. Here, we show that these interventions could work by reducing discrimination, bullying and marginalization. Interventions appear to work best when school staff are trained and the school climate is supportive and may be less effective for boys, gender minority students and bisexual students. Our findings provide guiding principles for schools to develop interventions and should encourage primary research to confirm, refute or refine our programme theories.
Reply to: Apolipoprotein C3 induces inflammasome activation only in its delipidated form
Authors: Stephen Zewinger, Jochen Reiser, Vera Jankowski, Dalia Alansary, Eunsil Hahm, Sarah Triem, Mira Klug, Stefan J. Schunk, David Schmit, Rafael Kramann, Christina Körbel, Emmanuel Ampofo, Matthias W. Laschke, Simina-Ramona Selejan, Anna Paschen, Tobias Herter, Susanne Gaul, Günther Silbernagel, Martina Sester, Urban Sester, Gunter Aßmann, Robert Bals, Gerhard Kostner, Willi Jahnen-Dechent, Michael D. Menger, Lucia Rohrer, Winfried März, Michael Böhm, Joachim Jankowski, Manfred Kopf, Eicke Latz, Barbara A. Niemeyer, Danilo Fliser, Ulrich Laufs, Thimoteus Speer
Journal: Nature Immunology (2023)
<i>ALK</i> Amplification and Rearrangements Are Recurrent Targetable Events in Congenital and Adult Glioblastoma
Authors: Anne-Florence Blandin, Ross Giglio, Maya Srikanth Graham, Guadalupe Garcia, Seth Malinowski, Jared K. Woods, Shakti Ramkissoon, Lori Ramkissoon, Frank Dubois, Kathleen Schoolcraft, Jessica Tsai, Dayle Wang, Robert Jones, Jayne Vogelzang, Kristine Pelton, Sarah Becker, Fiona Watkinson, Claire Sinai, Elizabeth F. Cohen, Matthew A. Booker, Michael Y. Tolstorukov, Veerle Haemels, Liliana Goumnerova, Karen Wright, Mark Kieran, Katie Fehnel, David Reardon, Arnault Tauziede-Espariat, Rishi Lulla, Benjamin Carcamo, Stanley Chaleff, Alain Charest, Frederik De Smet, Azra H. Ligon, Adrian Dubuc, Melanie Pages, Pascale Varlet, Patrick Y. Wen, Brian M. Alexander, Susan Chi, Sanda Alexandrescu, Ralf Kittler, Robert Bachoo, Pratiti Bandopadhayay, Rameen Beroukhim, Keith L. Ligon
Journal: Clinical Cancer Research (2023)

Abstract Purpose: Anaplastic lymphoma kinase (ALK) aberrations have been identified in pediatric-type infant gliomas, but their occurrence across age groups, functional effects, and treatment response has not been broadly established. Experimental Design: We performed a comprehensive analysis of ALK expression and genomic aberrations in both newly generated and retrospective data from 371 glioblastomas (156 adult, 205 infant/pediatric, and 10 congenital) with in vitro and in vivo validation of aberrations. Results: ALK aberrations at the protein or genomic level were detected in 12% of gliomas (45/371) in a wide age range (0–80 years). Recurrent as well as novel ALK fusions (LRRFIP1–ALK, DCTN1–ALK, PRKD3–ALK) were present in 50% (5/10) of congenital/infant, 1.4% (3/205) of pediatric, and 1.9% (3/156) of adult GBMs. ALK fusions were present as the only candidate driver in congenital/infant GBMs and were sometimes focally amplified. In contrast, adult ALK fusions co-occurred with other oncogenic drivers. No activating ALK mutations were identified in any age group. Novel and recurrent ALK rearrangements promoted STAT3 and ERK1/2 pathways and transformation in vitro and in vivo. ALK-fused GBM cellular and mouse models were responsive to ALK inhibitors, including in patient cells derived from a congenital GBM. Relevant to the treatment of infant gliomas, we showed that ALK protein appears minimally expressed in the forebrain at perinatal stages, and no gross effects on perinatal brain development were seen in pregnant mice treated with the ALK inhibitor ceritinib. Conclusions: These findings support use of brain-penetrant ALK inhibitors in clinical trials across infant, pediatric, and adult GBMs. See related commentary by Mack and Bertrand, p. 2567